The involvement of the central nervous system in syphilis may result in the development of overt neurologic manifestations or may remain asymptomatic for many years. Although many investigators have examined various parameters of CNS involvement, a comprehensive study correlating neurologic abnormalities, the presence of identifiable Treponema pallidum in the CSF, and modern methods for analysis of cerebrospinal fluid has not been performed. This study proposes to examine standard and new or rarely used tests for determination of neurologic involvement in syphilis infection. The presence of virulent T. palldium in CSF will be examined using the rabbit infectivity test; other measured CSF parameters will include cell counts, protein concentration, CSF-VDRL, FTA, and FTA-ABS testing, and measurements of blood-brain barrier function and intrathecal synthesis of treponemal antibody. The molecular specificities of CSF antibody for treponemal antigens will be examined using the Western blot technique. A complete neurologic examination will be performed, and subclinical neurologic dysfunction will be assessed using audiologic testing and auditory evoked potential testing. The persistence of T. pallidum in CSF following therapy with currently recommended regimens will be examined by rabbit infectivity testing; the correlation of these results with other CSF parameters will be analyzed. The normalization of all detected abnormalities will be followed post therapy. It is anticipated that these studies will contribute to a more complete understanding of asymptomatic and symptomatic CNS involvement in syphilis infection and may provide the clinician with needed guidelines for the evaluation and management of patients with all stages of syphilis.